During dauer diapause, precursor cells in developing tissues must remain quiescent and maintain their developmental potential over long periods of time. The canonical insulin/insulin-like signaling (IIS) pathway is a key regulator of dauer diapause; DAF-18/PTEN is an inhibitor of IIS, and DAF-16/FoxO is the main target. Dauer larvae lacking these components can be generated in
daf-7 mutants, which constitutively form dauers due to abrogation of a parallel dauer entry pathway (Vowels and Thomas 1992; Larsen et al. 1995). We will report our progress towards understanding the roles of these IIS components in maintaining quiescence and developmental potential in the somatic gonad and germline in dauer. First, in continuous development, LIN-12/Notch signaling is active in the Ventral Uterine precursor cells (VUs) from their birth until they divide in the mid-L3 stage; however, in dauer larvae, VUs do not divide and the LIN-12 transcriptional target
mir-61 is not expressed. These results suggest that LIN-12 signaling is blocked in the quiescent VUs, as it is in quiescent Vulval Precursor Cells (Karp and Greenwald 2013). Furthermore,
mir-61 is expressed in VUs in dauers lacking either DAF-18 or DAF-16 activity, suggesting that a canonical IIS pathway, in which DAF-18 activates DAF-16 through inhibition of IIS, is responsible for the block to LIN-12/Notch signaling in dauer. Second, we have observed that IIS components appear to have different roles in the maintenance of VU quiescence. In
daf-18 null mutant dauers, the VUs divide, indicating loss of quiescence, and their descendants express markers for the pi cell type, another indication that the block to LIN-12/Notch signaling is relieved (Newman et al. 1995). In contrast, the VUs rarely divide in
daf-16 null dauers, suggesting that DAF-18 does not regulate somatic gonad precursor cellular quiescence in dauer exclusively through IIS inhibition, or, alternatively, that IIS targets other than DAF-16 are required for regulating somatic gonad quiescence in dauer. Finally, we have been investigating the cellular focus for the requirement for
daf-18 in maintaining quiescence of somatic gonad precursors and the germline stem cells (GSCs) in dauer (Narbonne and Roy 2006, and our unpublished observations). Our mosaic analysis, tissue-specific rescue, and tissue-specific knockout experiments together suggest that DAF-18 non-autonomously coordinates both VU progression and germline quiescence in dauer from another cellular source.